Non-Vitamin K Antagonist Oral Anticoagulants (NOACs) Versus Warfarin in Patients with Atrial Fibrillation and (Morbid) Obesity or Low Body Weight: a Systematic Review and Meta-Analysis

Purpose: Oral anticoagulants are crucial for preventing systemic thromboembolism in atrial fibrillation (AF), with guidelines preferring non-vitamin K antagonist oral anticoagulants (NOACs) over vitamin K antagonists (VKAs) in the general AF population. However, as NOACs are administered in fixed doses, concerns of unintentional underdosing in morbidly obese patients and unintentional overdosing in underweight patients have emerged. Therefore, a critical appraisal of the benefit-risk profile of NOACs in AF patients across the body weight spectrum is needed. Methods and results: After searching Medline, this systematic review discusses the impact of body weight on the risk-benefit profile of NOACs versus VKAs. The meta-analysis demonstrated that NOAC use in obese and class III obese AF patients (body mass index (BMI) ≥ 30 and ≥ 40 kg/m2, respectively) was associated with significantly lower stroke/systemic embolism (stroke/SE) risks (RR 0.82, 95%CI [0.71-0.96] and RR 0.75, 95%CI [0.64-0.87], respectively), similar to lower major bleeding risks (RR 0.83, 95%CI [0.69-1.00] and RR 0.74, 95%CI [0.57-0.95], respectively) and similar mortality risks (RR 0.92, 95%CI [0.73-1.15] and RR 1.17, 95%CI [0.83-1.64], respectively) compared to VKAs. In AF patients ≤ 60 kg, significantly lower stroke/SE (RR 0.63, 95%CI [0.56-0.71]) and major bleeding risks (RR 0.71, 95%CI [0.62-0.80]), but similar mortality risks (RR 0.68, 95%CI [0.42-1.10]), were observed for NOAC- versus VKA-treated patients. Conclusion: The benefit-risk profile of NOACs seems preserved in (morbidly) obese AF patients and patients with low body weight. However, more data are needed on underweight AF patients (BMI < 18.5 kg/m2) and on differences between NOACs in these patients.